Michael Daniilidis

Haplotypes of human leukocyte antigens among patients with nasopharyngeal cancer in Greece

The concept that the major histocompatibility complex (MHC) plays an important role in the pathogenesis of nasopharyngeal cancer (NPC) in several ethnic groups has gained increased attention during the last 15 years. Earlier studies have suggested that an increased risk of NPC is associated with specific phenotypes of human leukocyte antigens (HLA). The present study was performed to examine the association of HLA specificities and haplotypes with NPC in a Greek population. In a genotypical study of 53 patients, a significant association between the haplotype HLA-B5DR11 and NPC was found, mainly in patients > 45 years. Also, the above haplotype was significantly associated with longer disease-free interval. HLA-B5 and HLA-B5DR11 were more often seen among patients with squamous cell histology than among those with the undifferentiated type. These results suggest that MHC loci are probably implicated in the pathogenesis and outcome of NPC in Greek patients.

Association between the heme oxygenase-1 promoter polymorphism and renal transplantation outcome in Greece.

BACKGROUND Heme oxygenase-1 (HO-1) is the enzyme that catabolizes heme into carbon monoxide, biliverdin, and free iron. The induction of this enzyme is an important cytoprotective mechanism, which occurs as an adaptive and beneficial response to a wide variety of oxidant stimuli. HO-1 has recently been suggested to protect transplants from ischemia/reperfusion and immunologic injury. HO-1 inducibility is mainly modulated by a (GT)(n) repeat polymorphism in the promoter region, and has been shown that short repeats (S) are associated with greater upregulation of HO-1, compared with long repeats (L). In the present study we investigated the influence of this HO-1 gene polymorphism on clinical outcome after transplantation and on renal transplant function. METHODS DNA from 175 donor/recipient pairs who underwent transplantation between October 2002 and June 2007 was genotyped. We divided the HO-1 alleles into 2 subclasses, the S ≤ 27 repeats and L > 27 repeats. RESULTS There has been significant relevance between the genotype of the donor and the outcome of the graft, as far as recipients with normal graft function and recipients with deteriorated graft function are concerned (P = .021). In patients with normal graft function, grafts from L-homozygotes were found in 24%, whereas in patients with deteriorated function, grafts from L-homozygotes exhibited in higher rate (50%). Neither the donors nor the recipients polymorphism influenced the graft survival (log-rank test P = .228 for the donors and log-rank test P = 0.844 for the recipients). There was no evidence of a gene-dose effect on graft survival (P = .469). Recipients of allografts from S-carriers donors had significantly lower serum creatinine levels at 24 months compared with recipients of allografts from L-homozygotes donors (P = .016).

The immune response in hemodialysis patients following physical training

The effects of mild physical training on the cell-mediated and humoral immune responses were studied in 18 patients with end-stage renal disease (6.5±5.2 years on hemodialysis) participating in a six month exercise renal rehabilitation program. They were matched with 14 untrained patients for sex, age, years on hemodialysis and causes of renal disease. Serum immunoglobulins (IgA, IgM, IgG), IgG subclasses (IgG1, IgG2, IgG3, IgG4), complement components (C3, C4), interleukins IL-2, IL-4, IL-6, subpopulations of T lymphocytes and panel reactive lymphocytotoxic antibodies were determined on all patients. By the end of the study, peak aerobic capacity (VO2 peak) was significantly improved by 42% in the trained group. This improvement was followed by a non-significant increase in IgE (by 13.8%) and in IgM (by 3%) and a decrease in IgA (by 17.5%, p<0.05), while the IgG levels remained constant. In the control group, there was no change in the levels of immunoglobulins. The values of interleukins, IgG subclasses, complement, lymphocytotoxic antibodies and T lymphocyte subsets remained almost unchanged in both groups. Finally, during the study, common upper respiratory infections were more often in the controls (58%), than in the trained patients (31%). The results suggest that physical training improves clinically the immune defense mechanisms in hemodialysis patients, although it does not significantly change cell-mediated and humoral immune responses.

Combined treatment with sitagliptin and vitamin D in a patient with latent autoimmune diabetes in adults.

Summary Latent autoimmune diabetes in adults (LADA) is a relatively new type of diabetes with a clinical phenotype of type 2 diabetes (T2D) and an immunological milieu characterized by high titers of islet autoantibodies, resembling the immunological profile of type 1 diabetes (T1D). Herein, we report a case of a young male, diagnosed with LADA based on both clinical presentation and positive anti-glutamic acid decarboxylase antibodies (GAD-abs), which were normalized after combined treatment with a dipeptidyl peptidase-4 inhibitor (DPP-4) (sitagliptin) and cholecalciferol. Learning points Anti-glutamic acid decarboxylase antibodies (GAD-abs) titers in young patients being previously diagnosed as type 2 diabetes (T2D) may help establish the diagnosis of latent autoimmune diabetes in adults (LADA). Sitagliptin administration in patients with LADA might prolong the insulin-free period. Vitamin D administration in patients with LADA might have a protective effect on the progression of the disease.

Postprandial response of bone turnover markers in patients with Crohn's disease.

AIM To investigate the postprandial response of bone turnover markers in patients with Crohns disease (CD). METHODS Fifty nine patients with CD aged 38 ± 14 years, and 45 healthy individuals matched for age and body mass index were included in the study. All participants underwent an oral glucose tolerance test (OGTT) after an overnight fast and serum levels of the bone resorption marker C-terminal crosslinking telopeptide of type I collagen (CTX-I) and the bone formation marker procollagen type I N propeptide were measured. Activity of the disease was assessed by calculation of the Crohns disease activity index (CDAI). RESULTS Serum CTX-I was significantly higher in patients compared to controls (CTX-I: 453 ± 21 pg/mL vs 365 ± 25 pg/mL, P = 0.008), and values were significantly correlated with the activity of the disease (r = 0.435, P = 0.001). Results from OGTT-induced suppression of CTX-I showed two different trends. Patients with more active disease (assessed as CDAI > 150) had a more excessive suppression of CTX-I compared to controls (55% vs 43% P < 0.001), while patients on remission (assessed as CDAI < 150) demonstrated an attenuated CTX-I suppression (30% vs 43% P < 0.001). In line with this, CTX-I suppression after oral glucose load was significantly correlated with the activity of the disease (r = 0.913, P < 0.001). CONCLUSION The physiological skeletal response of postprandial suppression of bone resorption is maintained in patients with CD and is strongly dependent to the activity of the disease.

Can HLA Typing Predict the Outcome of Grass Pollen Immunotherapy

Objective: The aim of this study was to investigate the relationship between HLA molecules and the positive or negative response of atopic patients to specific immunotherapy (SIT). Methods: We studied 42 atopic multisensitive patients undergoing grass pollen immunotherapy, 42 parents of patients (30 mothers and 12 fathers) and 173 control individuals. HLA class I and class II antigens were typed by a microlymphocytotoxicity test. The typing of DRB1* alleles for atopic patients and their parents was based on the reverse hybridization principle, while for the control group, DNA-RFLP and PCR-SSP methods were used. Results: The frequency of B14 and DRB1*1101-4 antigens/alleles, as well as the A2B5DR11 haplotype, showed a statistically significant difference in those patients who responded to immunotherapy. On the other hand, HLA-A28, B8 and DRB1*0301 antigens/alleles, as well as the frequency of the A1B8 and A1B8DR3 haplotypes, were found to be significantly higher in patients who responded poorly to SIT. Discussion: Our findings support the hypothesis that treatment responsiveness may show an association to HLA molecules, which could thus play a role in the immunological selection and monitoring of atopic patient candidacy for SIT.

The controversial impact of B cells subsets on immune response to pneumococcal vaccine in HIV-1 patients.

BACKGROUND Chronic HIV infection leads to severe perturbations of the B cell populations and hypo-responsiveness to vaccines. The associations between circulating B cell subpopulations and the antibody response to pneumococcal polysaccharide vaccine in antiretroviral-naïve and treated patients were studied. METHODS Sixty-six HIV-infected adults were grouped according to antiretroviral therapy (ART) and CD4+ cell count; 31 were ART-naïve and 35 were ART-treated, and they were matched for age, CD4 cell count, and duration of HIV infection. All subjects were immunized with the 23-valent polysaccharide vaccine against Streptococcus pneumoniae. Pre- and post-vaccination B cell subpopulations were assessed by flow cytometry. Serum IgG concentrations for vaccine serotypes were quantified by ELISA at baseline and at 4 and 48 weeks post-vaccination. RESULTS Patients under highly active antiretroviral therapy (HAART) had significantly higher antibody levels against pneumococcal vaccine antigens, while an adequate number of patients responded to vaccination. Memory B cells were diminished over time, although treated patients maintained higher levels of all subsets studied, with the exception of activated memory and isotype-switched memory B cells. CONCLUSIONS Low concentrations of total B cells and exhausted memory B cells was the strongest independent predictor of poor pneumococcal vaccine responsiveness, emphasizing that B cell subset disturbances are associated with a poor vaccine response among HIV-infected patients.

Thyroid Autoimmunity in the Context of Type 2 Diabetes Mellitus: Implications for Vitamin D

Vitamin D deficiency has been associated with both type 2 diabetes mellitus (T2DM) and autoimmune disorders. The association of vitamin D with T2DM and thyroid autoimmunity (TAI) has not been investigated. Thus, we aimed to explore the putative association between T2DM and thyroid autoimmunity (TAI) focusing on the role of 25-hydroxy-vitamin D (25(OH)D). Study population included 264 T2DM patients and 234 controls. To explore the potential association between 25(OH)D and thyroid autoimmunity while controlling for potential confounders—namely, age, gender, body mass index, and presence of T2DM—multivariate logistic regression analyses were undertaken. Patients with T2DM were younger (P < 0.001) and had significantly lower 25(OH)D levels (P < 0.001) and higher anti-TPO titers (P = 0.005). Multivariable logistic regression analyses suggested that T2DM and 25(OH)D levels were significantly associated with the presence of thyroid autoimmunity. In an elderly population of diabetic patients and controls with a high prevalence of vitamin D deficiency/insufficiency, a patient with T2DM was found to be 2.5 times more likely to have thyroid autoimmunity compared to a nondiabetic individual and the higher the serum 25(OH)D levels were, the higher this chance was.

HLA alleles and fissured tongue.

The aim of this study was to investigate the linkage between HLA and fissured tongue. Sixty‐ nine individuals with fissured tongue and 125 healthy volunteers were typed for HLA‐DRB1*. The results showed increased frequency of HLA‐DRB1*08 (P < 0.001), HLA‐DRB1*14 (P < 0.01), HLA‐DRB1*11 (P < 0.05) and HLA‐DRB1*16 (P < 0.05), while HLA‐DRB1*03 and HLA‐DRB1*07 frequency was decreased (P < 0.05).

Antiretroviral naive and treated patients: Discrepancies of B cell subsets during the natural course of human immunodeficiency virus type 1 infection

AIM To evaluate alterations of memory B cell subpopulations during a 48-wk period in human immunodeficiency virus type 1 (HIV-1) patients. METHODS Forty-one antiretroviral naïve and 41 treated HIV-1 patients matched for age and duration of HIV infection were recruited. All clinical, epidemiological and laboratory data were recorded or measured. The different B cell subsets were characterized according to their surface markers: Total B cells (CD19+), memory B cells (CD19+CD27+, BMCs), resting BMCs (CD19+CD27+CD21high, RM), exhausted BMCs (CD19+CD21lowCD27-, EM), IgM memory B (CD19+CD27+IgMhigh), isotype-switched BMCs (CD19+CD27+IgM-, ITS) and activated BMCs (CD19+CD21low+CD27+, AM) at baseline on week 4 and week 48. RESULTS Mean counts of BMCs were higher in treated patients. There was a marginal upward trend of IgM memory B cell proportions which differed significantly in the treated group (overall trend, P = 0.004). ITS BMC increased over time significantly in all patients. Naive patients had of lower levels of EM B cells compared to treated, with a downward trend, irrespectively of highly active antiretroviral therapy (HAART) intake. Severe impairment of EM B cells was recorded to both treated (P = 0.024) and naive (P = 0.023) and patients. Higher proportions of RM cells were noted in HAART group, which differed significantly on week 4th (P = 0.017) and 48th (P = 0.03). Higher levels of AM were preserved in HAART naive group during the whole study period (week 4: P = 0.018 and 48: P = 0.035). HIV-RNA viremia strongly correlated with AM B cells (r = 0.54, P = 0.01) and moderately with RM cells (r = -0.45, P = 0.026) at baseline. CONCLUSION HIV disrupts memory B cell subpopulations leading to impaired immunologic memory over time. BMC, RM, EM and ITS BMC were higher in patients under HAART. Activated BMCs (AM) were higher in patients without HAART. Viremia correlated with AM and RM. Significant depletion was recorded in EM B cells irrespectively of HAART intake. Perturbations in BMC-populations are not fully restored by antiretrovirals.